Acute myelogenous leukemia (AML) is a prevalent, deadly disease in older adults. Unlike the incidence rate of acute lymphoblastic leukemia (ALL) which stays pretty much the same among people of varying age groups, the incidence rate of AML shows a dramatic increase with increased age, suggesting a strong association between age and AML pathogenesis. The proposed research aims to (1) determine how two of the common mutations found in AML patients contribute to AML pathogenesis; (2) identify age-dependent factors that contribute to AML pathogenesis; and (3) validate potential, novel therapeutics against AML. The experiments will utilize various unique zebrafish models enabling inducible expression of the human oncogenes. The zebrafish has emerged as a powerful vertebrate model organism because it is highly amenable to both genetic and chemical perturbation. More than a dozen zebrafish mutants have been shown to recapitulate the characteristics of human hematological diseases, indicating that the hematopoietic system is highly conserved between zebrafish and humans. The proposed research will not only provide new insights into AML pathogenesis, but also lay a foundation for the use of zebrafish in studying the aging of the hematopoietic system. In addition, the proposed experiments will utilize novel chemical suppressors of the AML-like phenotype in zebrafish that we recently identified. Further characterization of these compounds may prove useful in the development of more effective and safer therapeutics against AML. The candidate has a background in cancer and molecular biology and now seeks to expand her scientific expertise and develop a research program centering around cancer, aging, and chemical biology. The candidate will conduct the research under the supervision of Dr. Randall Peterson. Dr. Peterson is known for his pioneering work on combining chemical genetic tools and zebrafish developmental biology for cardiovascular research. The candidate has also assembled a panel of advisors that include leaders in cancer, hemaotopoiesis, and aging. The sponsor and the advisors will closely interact with the candidate and guide her in both scientific and professional development. Ultimately, this program will facilitate the candidate's goals of becoming an independent investigator in cancer and aging. [unreadable] [unreadable] [unreadable]